Format

Send to

Choose Destination
Stem Cell Res Ther. 2014 Jun 6;5(3):74. doi: 10.1186/scrt463.

Substrate and strain alter the muscle-derived mesenchymal stem cell secretome to promote myogenesis.

Abstract

INTRODUCTION:

Mesenchymal stem cells (MSCs) reside in a variety of tissues and provide a stromal role in regulating progenitor cell function. Current studies focus on identifying the specific factors in the niche that can alter the MSC secretome, ultimately determining the effectiveness and timing of tissue repair. The purpose of the present study was to evaluate the extent to which substrate and mechanical strain simultaneously regulate MSC quantity, gene expression, and secretome.

METHODS:

MSCs (Sca-1+CD45-) isolated from murine skeletal muscle (muscle-derived MSCs, or mMSCs) via fluorescence-activated cell sorting were seeded onto laminin (LAM)- or collagen type 1 (COL)-coated membranes and exposed to a single bout of mechanical strain (10%, 1 Hz, 5 hours).

RESULTS:

mMSC proliferation was not directly affected by substrate or strain; however, gene expression of growth and inflammatory factors and extracellular matrix (ECM) proteins was downregulated in mMSCs grown on COL in a manner independent of strain. Focal adhesion kinase (FAK) may be involved in substrate regulation of mMSC secretome as FAK phosphorylation was significantly elevated 24 hours post-strain in mMSCs plated on LAM but not COL (P <0.05). Conditioned media (CM) from mMSCs exposed to both LAM and strain increased myoblast quantity 5.6-fold 24 hours post-treatment compared with myoblasts treated with serum-free media (P <0.05). This response was delayed in myoblasts treated with CM from mMSCs grown on COL.

CONCLUSIONS:

Here, we demonstrate that exposure to COL, the primary ECM component associated with tissue fibrosis, downregulates genes associated with growth and inflammation in mMSCs and delays the ability for mMSCs to stimulate myoblast proliferation.

PMID:
24906706
PMCID:
PMC4097833
DOI:
10.1186/scrt463
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center